It is estimated that more than thirty million people each year are treated for respiratory diseases such as asthma and cystic fibrosis by aerosolizing medication in disposable, small-volume nebulizers, following which the medicine is then inhaled by a patient as a part of the patient's therapy. Bronchodilators, such as albuterol sulfate or ipratropium bromide, are typically used in order to improve airflow among patients with pulmonary maladies. Additional medicines, used in different forms of therapy or to treat different maladies, are also possible. As used herein, the terms “medicine” and “medication” shall refer to any one or a combination of substances used primarily in patient treatment and specifically excluding substances such as saline solution or water used primarily for the humidification of gases inhaled by a patient.
Pharmaceutical companies originally packaged these medicines in containers that held multiple doses. In order to initiate a patient treatment, the medicine needed to be transferred from the container to the treatment equipment such as a nebulizer. As the containers were repeatedly opened and closed, the medicine was exposed to bacterial contamination. In order to stem bacterial growth, chemicals such as benzalkonium chloride, or BAC, were added. However, it was eventually found that BAC itself may lead to airway constriction. See, Meyer, Harriet, “Antibacterial Agent In Some Asthma Medications Linked To Airway Constriction, UF Scientists Find.” UF News, Jan. 11, 2001. Thus, the use of BAC may have negated or at least reduced any positive effect the bronchodilators may have had.
In order to reduce bacterial contamination without adding potentially harmful antibacterial chemicals, pharmaceutical manufacturers began to package respiratory drugs in single-dose or “unit-dose” containers, thus removing the need to repeatedly open a container of medicine to dispense a dose. These unit-dose respiratory drugs are typically packaged in soft plastic containers often formed from low density polyethylene, or LDPE, in order to help control costs and to make the containers easy to open.
Typically, the medication is opened by twisting the top of the unit-dose container until the plastic gives way at a thin portion of plastic at the neck. The medication is then transferred into a disposable nebulizer by aiming the unit-dose container opening at the nebulizer housing opening, squeezing the soft plastic of the container until the contents have emptied, and then disposing of the empty unit-dose container.
However, unit-dose packaging was found to have inherent drawbacks. First, packaging costs increased over the previous bulk packaging due to the fact that each dose necessitated its own container. Second, the mere fact that the medicine must be transferred from a packaging container to a nebulizer or other treatment device is believed to carry an inherent risk of contamination. Further, it was found that LDPE is permeable to chemicals that have moderate to high vapor pressure, such as adhesives, varnishes, inks, and solvents, all of which are typically used in labeling and packaging materials. After it was determined that a number of different inhalation drugs packaged in LDPE unit-dose containers were contaminated with these chemicals, the industry moved away from printed paper-and-ink labels to embossed labeling with raised lettering. See, Grissinger, Matthew, “Errors in the Making: Nearly Unreadable Labeling of Plastic Ampules for Nebulizing Agents.” Medication Errors; P&T Journal May 2005; Vol. 30, No. 5, pp. 255-58.
Unfortunately, medication errors due to the poor legibility of embossed lettering on LDPE unit-dose containers have caused great concern in the medical community. See, Grissinger, Id. Drug names, concentrations, lot numbers, and expiration dates are embossed into the containers in the form of transparent, raised letters rendering them virtually impossible to read. This leads all too frequently to administering the wrong drug. Mistakes occur when unit-dose respiratory drugs are stored in refrigerated “respiratory bins” where a number of different drugs are typically placed. The risk of using the wrong medication is also increased when clinicians keep various unit-dose medications in their laboratory coat pockets, which is often the case.
The problem of potential medication errors associated with embossed labeling on unit-dose containers continues. Transferring medication from unit-dose containers takes time, adds to difficulty of use, introduces the potential for contamination during transfer, and runs the risk of under-dosing due to spillage. In addition, there still remains the added packaging cost associated with packaging each dose separately, not to mention environmental concerns associated with the disposal of millions of plastic unit-dose containers. Finally, even though LDPE plastic containers are more malleable than other plastics, these containers are still difficult to open, especially for elderly and arthritic patients.
Thus, there remains a need for packaging system for liquid medicines, which may be clearly labeled without risk of label-chemical contamination, which reduces the risk of contamination during transfer of medication from container to nebulizer, which reduces or eliminates the cost associated with each dose needing its own individual container, which saves the time associated with transferring medication from container to nebulizer, which reduces the need for disposal of millions of plastic unit-dose containers, which reduces the risk of under-dosing due to spillage, and which may still be more easily opened or used by elderly and arthritic patients.
Medical nebulizers are divided into two general categories: 1) large-volume, and 2) small-volume. Large-volume nebulizers are used, most often in hospital settings, to humidify gas, usually oxygen, to a patient. Large-volume nebulizers are utilized to add moisture to otherwise very dry gas by aerosolizing water, usually sterilized water with some mixture of saline in order to mimic the human body's salt content. Large-volume nebulizers often come pre-filled with various mixtures of sterile water and saline. Large-volume nebulizers have a reservoir volume greater than 100 mL. See Bruce K. Rubin & James B. Fink, Aerosol Therapy for Children, in 7 No. 2 RESPIRATORY CARE CLINICS OF NORTH AMERICA: AEROSOL THERAPY, 175, 187 (James B. Fink & Rajiv Dhand eds. 2001).
Small-volume nebulizers, also referred to as “hand-held nebulizers,” are used for delivering medication to the lungs. Small-volume nebulizers are powered by high-pressure air or oxygen and are classified as pneumatic jet nebulizers. These devices are used for aerosolized medication therapy in both home and hospital settings. Although small-volume nebulizers are utilized in the delivery of a number of medications from analgesics to antibiotics, they are most often used to administer bronchodilators. Because they are for drug administration rather than humidification, small-volume nebulizers have medication reservoirs of 10 to 15 mL or less.
Small-volume nebulizers have come under scrutiny in recent years because of bacterial contamination. Traditionally, it has been common practice to clean and re-use disposable, single-patient-use, small-volume nebulizers. However, unless the nebulizer is completely sterilized it has been found that these “cleaned” nebulizers run the risk of growing such pathogens as Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae, as well as other dangerous organisms. It is believed that contamination of the nebulizer occurs not only in spite of the cleaning, but may indeed be due to the cleaning itself. It is thought that poor cleaning techniques, inadequate drying, and the use of potable water sources may contribute to the contamination. Because of the risk of contamination and the fact that small-volume nebulizers are relatively inexpensive, especially when compared to the cost of nosocomial infections, many hospitals have come to the conclusion that it is safer and more prudent to dispose of the small-volume nebulizer soon after use. For example, it is currently a practice in many hospitals to utilize the same disposable nebulizer for twenty-four hours without cleaning, and then to dispose of it. See, O'Malley, Catherine A, et al. “A Day in the Life of a Nebulizer: Surveillance for Bacterial Growth in Nebulizer Equipment of Children With Cystic Fibrosis in the Hospital Setting.” Respiratory Care 2007, Vol. 52, No. 3, pp. 258-62.
Respiratory patients are often treated with physiotherapies, physical therapies without medication, for the purposes of opening the airways, assisting in increased bi-level flow to enhance secretion movement, and to strengthen diaphragm muscles. These therapies generally fit into one of two categories depending upon the source of flows and pressures utilized in the therapy. One such category of devices utilizes flow and pressure generated by an external apparatus, such as intermittent positive pressure breathing devices (IPPB) such as the Mark 7®, MetaNeb®, or The Vest®. Each of these devices mechanically generates the flows and pressures necessary for the therapy. This category of device is more costly and intended for patients with a higher acuity level, many of whom do not have the ability to supply their own flows and pressures sufficiently to be effective.
The other category utilizes the flow and pressure generated by the patient. Examples of device in this category are positive expiratory pressure, Aerobika™, and Flutter®. Therapies that depend on flows and pressures created by the patient use either constant or intermittent resistance to the patient's flow. Positive expiratory pressure (PEP) is a constant resistance to patient exhalation, keeping backpressure on airways to keep them open. Some PEP devices also oscillate and are known as “oscillating positive expiratory pressure” (OPEP). Flutter® is another form of OPEP. The devices in this category are usually less costly and intended for those patients with less acuity and still strong enough to supply their own flow for the therapy.
The demands of the healthcare industry require devices and methods that deliver therapies appropriate to the patient's acuity, which cost less, require less time, and maximize efficacy. To this end, there are problems with the scarcity of choices among existing devices and methods for delivering these therapies.
Some small-volume nebulizers generate great variability in particle sizes, or heterodispersal, during the conversion of liquid medication into aerosol. Since various particle sizes tend to deposit in different locations within the lungs, it is desirable to reduce a wide variability of particle sizes to a tighter, more consistent size-range range, making the aerosol more monodispersed.
In addition, small-volume nebulizers waste medication during the exhalation phase of the breathing cycle. The medication is lost during a treatment in relation to the person's inspiratory to expiratory (I:E) ratio which typically ranges from 1:2 to 1:3. That is, if a patient has an I:E ratio of 1:2, for every 1 second the patient inhales 2 seconds are required to exhale. Accordingly, a small-volume nebulizer that creates continuous aerosol only delivers 1 second, or ⅓, of that aerosol to the patient and the remaining 2 seconds, or ⅔, is exhaled into the atmosphere. This waste of medication serves to further escalate the overall cost of healthcare to society.
Some research appears to indicate that healthcare workers, especially nurses and respiratory therapists, have a higher incidence of breathing maladies, such as asthma, than do other professionals. There is concern that these clinicians who work in environments where the delivery of aerosolized medications is commonplace may be put at risk by being forced to breathe the otherwise wasted medication mentioned above that remains suspended in ambient air.
Attempts have been made to create small-volume nebulizers that produce aerosol only during the inspiratory phase of the breath by utilizing complex valve systems that divert a high-pressure source gas away from the aerosolizing chamber. Other attempts to reduce the loss of medication include adding a series of one-way valves and additional reservoirs to retain the aerosol being produced during the patient's expiratory phase so that it can be delivered in a large bolus and the beginning of the next inspiratory phase of breath. Examples of these attempts are to be seen in a breathing circuit apparatus with a 50 cc reservoir (U.S. Pat. No. 5,584,285) and a reservoir bag apparatus (U.S. Pat. No. 6,390,090). However, the complexity of design increases the number parts to be manufactured as well as increasing the labor of assembly, thus increasing the cost of the device from existing small-volume nebulizers. In addition, the additional reservoirs and/or reservoir volume present the problem of additional surface area to which the aerosol can adhere, thus still wasting medication. In addition, the increased complexity and components may increase the likelihood of malfunctions in the operation of the device.
Another problem with delivering medication and non-medication therapies is the paucity of single devices that have the ability to deliver multiple therapies inexpensively. If a patient is deemed to require both medicated aerosol therapy and PEP physiotherapy typically two separate devices must be used. The need to use multiple devices to deliver the therapies results in added cost, added training time, added storage space, and may lead to an increased likelihood of contamination.
Attempts to combine physiotherapy devices and nebulizers, such as an oscillating PEP device (U.S. Pat. No. 8,539,951) and a small-volume nebulizer designed to manufacture aerosol only during inspiration (U.S. Pat. No. 6,044,841), require significant complexity and resulting high cost. In addition, the increased complexity may increase the likelihood of malfunctions in the operation of the device.